Cytokeratin‐20 and seminal vesicle secretory protein VI as possible marker proteins in urinary bladder preneoplastic lesions induced by N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine

Abstract

Background : A simple and non-invasive methods for the diagnosis of transitional cell carcinoma of the bladder are needed for the prevention of invasive tumor. A proteomic technology has recently been developed to facilitate protein profiling of biological mixtures. We tried to detect the marker proteins by proteomic approach during the initiation stages on N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis in rats. Methods : Ten rats in group A were given 0.05% BBN in drinking water for 12 weeks. Other 10 rats in group B with 10 rats were designated as a control group and were not given BBN. Whole urinary bladders of all rats were excised at 12 weeks from the beginning of the experiment. Conventional proteomics was performed with high resolution 2-dimension gel electrophoresis followed by computational image analysis and protein identification using mass spectrometry. Results : A comparison of urinary bladder hyperplasia tissue with control tissue showed that five proteins; actin γ 2 propeptide, cytokeratin-20 (CK-20), proapolipoprotein, α 2 actin ( α -cardiac actin) and heat shock 27 kDa protein-1 were over-expressed in hyperplastic tissues. Three proteins; transcription factor myocardin, seminal vesicle secretory protein VI (SVS-VI) precursor and hypothetical protein RMT-7 were under-expressed in hyperplastic tissues. Conclusion : In our animal mode, BBN-induced urinary bladder mucosal hyperplasia resulted in an increase in the expression of five proteins and a decrease in the expression of three proteins. Of these, CK-20 and SVS-VI seem to be of particular interest. However other method such as Western blotting seems to be needed for confirmation of these proteins and more information on human bladder tissue is needed for clinical application.

Clinical, prognostic, and therapeutic significance of heat shock protein 27 in bladder cancer

“…Results of several studies regarding the prognostic potential of HSP27 have conflicted. For example, in an N-butyl-N-(4-hydroxybutyl) nitrosamine-induced BC animal model, HSP27 was overexpressed in hyperplastic tissue relative to that in control tissues [ 17 ]. In 75 schistosomiasis-associated BC cases, 45 (60%) patients showed HSP27 expression, and a significant correlation was found between expression of HSP27 and tumor grade, stage, and recurrence [ 18 ].…”

“…The exact reasons for these conflicting results remain unclear. However, it is noteworthy that most prior studies on the clinicopathological and prognostic significance of HSP27 expression in BC were based on a small number of patients [ 18 , 20 , 21 ] and included either an animal model [ 17 ] or BC cell lines [ 19 ] only, without examining patient-derived samples.…”

“…However, HSP27 expression in BC has not been investigated extensively, and its clinical and functional roles in BC are controversial. Several studies have reported significant associations between HSP27 expression and BC aggressiveness or patient prognosis [ 17 – 19 ], whereas other studies have shown contradictory results, with no such associations found [ 20 – 22 ].…”

“…However, in those studies suggesting therapeutic effects of OGX-427 in BC [ 28 , 29 ], OGX-427 alone did not significantly affect BC cell viability or apoptosis, showing only a non-significant trend of tumor suppression. Besides conflicting results regarding the clinical significance of HPS27 in BC [ 17 – 22 , 28 , 29 ], these findings indicate that although OGX-427 can enhance sensitivity to other chemotherapeutic agents, its therapeutic role is uncertain.…”

Challenges of Genomics and Proteomics in Nephrology

“…In experimentally induced TCC in rats, two proteins emerged as potentially valuable markers: cytokeratin-20 (CK-20), which was over-expressed, and seminal vesicle secretary protein VI (SVS-VI), which was under-expressed in hyperplastic tissues. [51] The inflammation-associated calcium binding protein S100A8 (MRP-8, calgranulin A) is reported to be highly expressed in tumor cells in contrast to normal urothelium. [52] These new markers, when fully characterized, may contribute to new target proteins for the prediction of aggressive, invasive bladder tumors.…”